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Lattice Ultrasensitivity Amplifies Signals in E. coli without Finely-Tuned Allosteric Interactions

Derek M. Sherry1,2, Isabella R. Graf1,2,3,4,*, Samuel J. Bryant1, Thierry Emonet1,2,5,†, and Benjamin B. Machta1,2,‡

  • *Contact author: isabella.graf@embl.de
  • †Contact author: Thierry.emonet@yale.edu
  • ‡Contact author: benjamin.machta@yale.edu
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PRX Life 4, 023027 – Published 8 June, 2026

DOI: https://doi.org/10.1103/7dgz-l5fd

Abstract

The E. coli chemosensory lattice, consisting of receptors, kinases, and adaptor proteins, is an important test case for biochemical signal processing. Kinase output is characterized by precise adaptation to a wide range of background ligand levels and large gain in response to small relative changes in concentration. Existing models of this lattice achieve their gain through allosteric interactions between either receptors or core units of receptors and kinases. Here we introduce a model which operates through an entirely different mechanism in which receptors gate inherently far from equilibrium enzymatic reactions between neighboring kinases. Our lattice model achieves gain through a mechanism more closely related to zero-order ultrasensitivity than to allostery. Thus, we call it lattice ultrasensitivity (LU). Unlike other lattice models with critical points, the LU model can achieve arbitrarily high gain through timescale separation, rather than through finely tuned allosteric interactions. The model also captures qualitative experimental results which are difficult to reconcile with existing models. We discuss possible implementations in the lattice's baseplate where long flexible linkers could potentially mediate interactions between neighboring core units.

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PRX Life 4, 023027– Published 8 June, 2026
  • Received 14 March 2025
  • Accepted 11 March 2026
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Published by the American Physical Society under the terms of the Creative Commons Attribution 4.0 International license. Further distribution of this work must maintain attribution to the author(s) and the published article's title, journal citation, and DOI.

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